β-Amyloid Accumulation in RPE Lysosomes

Article: New study links protein causing Alzheimer’s disease with common sight loss
Source: University of Southampton, via ScienceDaily
Published: March 10, 2021

Researchers in the U.K. recently published a study linking age-related macular degeneration (AMD) with the accumulation of β-amyloid proteins in the lysosomes of retinal pigment epithelial (RPE) cells. Beta amyloid is a hallmark of Alzheimer's disease, so this study also makes a connection between Alzheimer's and AMD, guided by prior research findings that donor eyes from patients who had suffered from AMD showed high levels of β-amyloid in their retinas. In their particular mouse model, the researchers were able to introduce β-amyloid to the mouse eyes, which subsequently developed retinal pathology similar to AMD in humans, without the use of transgenic mice. Though the lead researcher states that reducing the use of transgenic animals improves animal welfare, mouse models were still used, with the greatest practical benefit being a reduction in time to produce. More importantly, the researchers also used in vitro cell models to investigate the effect of β-amyloid on RPE cells. They found that β-amyloid accumulated in RPE cell lysosomes, and once invaded by β-amyloid, there were 20% fewer lysosomes available to perform recycling of photoreceptor discs, a necessary daily clean up process for vision at the cellular level. The experiments also found that once β-amyloid entered RPE cells, 85% of these toxic proteins remained in the lysosomes (rather than are cleared away) and accumulate over time. The finding of β-amyloid accumulation in RPE cells, thus linking AMD and Alzheimer's disease, seems to be a new connection that could guide additional anti-amyloid therapy pathways for both diseases.

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